Gelbard Maya K, Grace Miranda, von Schoeler-Ames Annika, Gnanou Ida, Munger Karl
Genetics, Molecular, and Cellular Biology Program, Graduate School of Biomedical Sciences, Tufts University, 02111, Boston, MA, USA; Department of Developmental, Molecular and Cellular Biology, Tufts University School of Medicine, 02111, Boston, MA, USA.
Department of Developmental, Molecular and Cellular Biology, Tufts University School of Medicine, 02111, Boston, MA, USA.
Tumour Virus Res. 2024 Dec 5;19:200300. doi: 10.1016/j.tvr.2024.200300.
Human papillomaviruses (HPVs) are a diverse family of viruses with over 450 members that have been identified and fully sequenced. They are classified into five phylogenetic genera: alpha, beta, gamma, mu, and nu. The high-risk alpha HPVs, such as HPV16, have been studied the most extensively due to their medical significance as cancer-causing agents. However, while nearly 70% of all HPVs are members of the gamma genus, they are almost entirely unstudied. This is because gamma HPVs have been considered medically irrelevant commensals as most of them infect the skin and are not known to cause significant clinical lesions in immunocompetent individuals. Members of the gamma 6 HPVs, however, have been detected in the anogenital tract mucosa and HPV101 has been isolated from a premalignant cervical lesion. Moreover, gamma 6 HPVs have a unique genome structure. They lack E6 proteins but in place of E6, they encode unique, small hydrophobic proteins without any close viral or cellular homologs that have been termed E10. Here, we report that HPV101 E7 shares biochemical activities with the high-risk alpha HPV16 E7, including the ability to target the pRB and PTPN14 tumor suppressors for degradation. This study underscores the importance of further characterizing HPV101 and other unstudied HPV species.
人乳头瘤病毒（HPV）是一个多样化的病毒家族，已鉴定并完成全序列测定的成员超过450种。它们被分为五个系统发育属：α、β、γ、μ和ν。高危α型HPV，如HPV16，由于其作为致癌因子的医学意义，研究最为广泛。然而，虽然所有HPV中近70%是γ属成员，但它们几乎完全未被研究。这是因为γ型HPV被认为是医学上无关的共生菌，因为它们大多数感染皮肤，并且在免疫功能正常的个体中不会引起明显的临床病变。然而，已在肛门生殖道黏膜中检测到γ6型HPV的成员，并且已从癌前宫颈病变中分离出HPV101。此外，γ6型HPV具有独特的基因组结构。它们缺乏E6蛋白，但取而代之的是，它们编码独特的小疏水蛋白，没有任何紧密的病毒或细胞同源物，这些蛋白被称为E10。在此，我们报告HPV101 E7与高危α型HPV16 E7具有相同的生化活性，包括靶向pRB和PTPN14肿瘤抑制因子进行降解的能力。这项研究强调了进一步鉴定HPV101和其他未研究的HPV种类的重要性。
